Glucagon-Like Peptide-1 Receptor Agonists in Post-bariatric Surgery Patients: A Systematic Review and Meta-analysis.

BACKGROUND: A significant number of patients face the issue of weight gain (WG) or inadequate weight loss (IWL) post-bariatric surgery for obesity. Several studies have been published evaluating the role of glucagon-like peptide-1 receptor agonists (GLP1RA) for weight loss post-bariatric surgery. However, no systematic review and meta-analysis (SRM) till date has evaluated the efficacy, safety and tolerability of GLP1RA in this clinical scenario. Hence, this SRM aimed to address this knowledge gap. METHODS: Databases were searched for randomized controlled trials (RCTs), case-control, cohort and observational studies involving use of GLP1RA in the intervention arm post-bariatric surgery. Primary outcome was weight loss post at least 3 months of therapy. Secondary outcomes were evaluation of body composition parameters, total adverse events (TAEs) and severe adverse events (SAEs). RESULTS: From initially screened 1759 articles, 8 studies (557 individuals) were analysed. Compared to placebo, patients receiving liraglutide had significantly greater weight loss after 6-month therapy [MD - 6.0 kg (95% CI, - 8.66 to - 3.33); P < 0.001; I2 = 79%]. Compared to liraglutide, semaglutide had significantly greater percent reduction in body weight after 6-month [MD - 2.57% (95% CI, - 3.91 to - 1.23); P < 0.001; I2 = 0%] and 12-month [MD - 4.15% (95% CI, - 6.96 to - 1.34); P = 0.004] therapy. In study by Murvelashvili et al. (2023), after 12-month therapy, semaglutide had significantly higher rates of achieving > 15% [OR 2.15 (95% CI, 1.07-4.33); P = 0.03; n = 207] and > 10% [OR 2.10 (95% CI, 1.19-3.71); P = 0.01; n = 207] weight loss. A significant decrease in fat mass [MD - 4.78 kg (95% CI, - 7.11 to - 2.45); P < 0.001], lean mass [MD - 3.01 kg (95% CI, - 4.80 to - 1.22); P = 0.001] and whole-body bone mineral density [MD - 0.02 kg/m2 (95% CI, - 0.04 to - 0.00); P = 0.03] was noted with liraglutide. CONCLUSION: Current data is encouraging regarding use of GLP1RAs for managing WG or IWL post-bariatric surgery. Deterioration of bone health and muscle mass remains a concern needing further evaluation. TRIAL REGISTRATION: The predefined protocol has been registered in PROSPERO having registration number of CRD42023473991.

Expert eValuation of Efficacy and Rationality of Vildagliptin "EVER-Vilda": An Indian Perspective.

Vildagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor is effective in reducing HbA1c levels in patients with type 2 diabetes (T2DM) when administered as monotherapy, dual or triple combination therapy. In India, Vildagliptin is commonly prescribed in T2DM patients because it reduces mean amplitude of glycemic excursion (MAGE), has lower risk of hypoglycemia and is weight neutral. Early combination therapy with vildagliptin and metformin is effective and well-tolerated in patients with T2DM, regardless of age or ethnicity. In view of already existing data on vildagliptin and the latest emerging clinical evidence, a group of endocrinologists, diabetologists and cardiologists convened for an expert group meeting to discuss the role and various combinations of vildagliptin in T2DM management. This practical document aims to guide Physicians and Specialists regarding the different available strengths and formulations of vildagliptin for the initiation and intensification of T2DM therapy.

Hyperprolactinemia Due to Prolactinoma has an Adverse Impact on Bone Health with Predominant Impact on Trabecular Bone: A Systematic Review and Meta-Analysis.

BACKGROUND: No meta-analysis has holistically analysed and summarized the effect of prolactin excess due to prolactinomas on bone mineral metabolism. We undertook this meta-analysis to address this knowledge-gap. METHODS: Electronic databases were searched for studies having patients with hyperprolactinemia due to prolactinoma and the other being a matched control group. The primary outcome was to evaluate the differences in BMD Z-scores at different sites. The secondary outcomes of this study were to evaluate the alterations in bone mineral density, bone mineral content and the occurrence of fragility fractures. RESULTS: Data from 4 studies involving 437 individuals was analysed to find out the impact of prolactinoma on bone mineral metabolism. Individuals with prolactinoma had significantly lower Z scores at the lumbar spine [MD -1.08 (95 % CI: -1.57 - -0.59); P < 0.0001; I2 = 54 % (moderate heterogeneity)] but not at the femur neck [MD -1.31 (95 % CI: -3.07 - 0.45); P = 0.15; I2 = 98 % (high heterogeneity)] as compared to controls. Trabecular thickness of the radius [MD -0.01 (95 % CI: -0.02 - -0.00); P = 0.0006], tibia [MD -0.01 (95 % CI: -0.02 - -0.00); P=0.03] and cortical thickness of the radius [MD -0.01 (95 % CI: -0.19 - -0.00); P = 0.04] was significantly lower in patients with prolactinoma as compared to controls. The occurrence of fractures was significantly higher in patients with prolactinoma as compared to controls [OR 3.21 (95 % CI: 1.64 - 6.26); P = 0.0006] Conclusion: Bone mass is adversely affected in patients with hyperprolactinemia due to prolactinoma with predominant effects on the trabecular bone.

Ulinastatin Add-on to Standard of Care in Critically Ill COVID-19 Patients: A Multicenter, Retrospective Study.

AIM: To assess the impact on 30-day mortality with ulinastatin (ULI) used as add-on to standard of care (SOC) compared to SOC alone in coronavirus disease (COVID-19) patients requiring admission to the intensive care unit (ICU). MATERIALS AND METHODS: In this multicentric, retrospective study, we collected data on clinical, laboratory, and outcome parameters in patients with COVID-19. Thirty-day mortality outcome was compared among patients treated with SOC alone and ULI used as add-on to SOC. Odds ratio (OR) and 95% confidence intervals (CI) were determined to identify the predictors of 30-day mortality. RESULTS: Ninety-four patients were identified and enrolled in both groups with comparable baseline parameters. On univariate analysis, 30-day mortality was significantly lower in ULI plus SOC group than SOC alone group (36.2 vs 51.1%, OR 0.54, 95% CI 0.30-0.97, p = 0.040). The effect on mortality was more pronounced in patients who did not require intubation (10.9 vs 34.0%, OR 0.24, 95% CI 0.09-0.66, p = 0.006) and with early administration (within 72 hours of admission) of ULI (30.7 vs 57.9%, OR 0.32, 95% CI 0.11-0.91, p = 0.032). On multivariate analysis, only intubation predicted mortality (adjusted OR 10.13, 95% CI 3.77-27.25, p<0.0001) and the effect of ULI on survival was not significant (adjusted OR 0.58, 95% CI 0.22-1.52, p = 0.270). CONCLUSION: Given the limited options for COVID-19 patients treated in ICU, early administration of ULI may be helpful, especially in patients not requiring intubation to improve the outcomes. Further, a large, randomized study is warranted to confirm these findings.

Primary Care Screening Tool for Polycystic Ovary Syndrome: Step One in the Battle Against Non-Communicable Disease.

Polycystic ovary syndrome (PCOS) is often the first manifestation, in adolescents and young adults, of metabolic problems that may occur later. Early identification, timely referral and appropriate treatment can result in improved reproductive, metabolic and comprehensive health. However, unlike other components of metabolic syndrome, which can be diagnosed at primary care level, there is no inexpensive, clinical tool to screen for PCOS. We share a simple six-item questionnaire, structured in three domains, which can be used as a screening tool for the syndrome. This allows early diagnosis and management of the condition, facilitates a life course approach to health promotion, and lays the foundation for the prevention of other comorbid metabolic disorders. It also helps integrate national programmes concerning non-communicable disease and women's healthcare under one umbrella, thus optimizing and strengthening delivery of community care.

Osteoporosis and diabetes: The dual pandemics.

Bone health is an important, but neglected aspect of diabetes care. People with type 1 diabetes are known to have a lower bone mineral density (BMD), which put them at a greater risk of osteoporosis and fractures. While BMD in those with type 2 diabetes is often misleading, multiple factors operate to increase the risk of falls and fractures in them. This article provides an overview of osteoporosis in diabetes. It proposes a LEMON mnemonic to understand the multifaceted aspects of bone care.

Counselling for Testosterone Therapy in Mid Life Men.

Testosterone is frequently used for the optimization of mid-life health. This therapy is effective and safe if accompanied by adequate counseling, before prescription, and during administration. In this opinion piece, we discuss the style and substance of medication counseling for testosterone therapy. The role and scope of counseling are highlighted, with a focus on screening, diagnosis, medication counseling, sexual counseling, and monitoring. This article should prove useful for all health care professionals.

Retrospective Cohort Observational Study to compare the Effect of Mycobacterium w along with Standard of Care vs Standard of Care alone in critically ill COVID-19 Patients.

BACKGROUND: COVID-19 has created enormous health crisis in India due to limited available treatments. Majority of the physicians use sepsis as a prototype to understand the pathophysiology of COVID-19 as there are similarities. Heat-killed Mycobacterium w (Mw) (Inj. Mw®) is a known immunomodulator, which is approved for the treatment of gram-negative sepsis. This observational study was aimed to evaluate the role of Mw along with standard of care (SOC) in critically ill COVID-19 patients. METHODS: Total 448 patients' data (intervention group: 298 in Mw plus SOC vs 150 in SOC alone) with reverse transcriptase-polymerase chain reaction (RT-PCR) confirmed critically ill COVID-19 patients who were admitted at five tertiary care centers were evaluated. They were observed for changes in laboratory [C-reactive protein (CRP), D-dimer, ferritin, lactate dehydrogenase (LDH), and interleukin-6 (IL-6)] parameters, hospital stay, intensive care unit (ICU) stay, and discharge status after giving 0.3 mL intradermal Mw for 3 consecutive days along with SOC during hospitalization. Standard of care included injectable steroids, remdesivir, and heparin. Data were analyzed using STATA 14.2 (StataCorp., College Station, Texas, USA). RESULTS: In baseline characteristics, Mw plus SOC arm had more critically ill patients as seen by higher high-resolution computed tomography (HRCT) score, higher lab values [CRP, ferritin, D-dimer, LDH, creatinine, alanine aminotransferase (ALT)], and more oxygen requirement as compared to SOC alone. Mycobacterium w arm had significantly higher mortality rate in ICU and hospital. Both hospital stay and ICU stay were longer in Mw arm. However, subgroup analysis found that early initiation of Mw (<3 days vs >3 days) was associated with significantly lesser odds of mortality and lesser odds of intubation requirement. Early initiation of Mw (<3 days vs >3 days) also resulted in significantly lesser duration of stay in the ICU along with reduction of CRP, D-dimer, and LDH. Moreover, further analysis of early initiation of Mw (<3 days vs control) resulted in significant reduction in lab values (procalcitonin, CRP, ferritin, LDH, and D-dimer). CONCLUSION: Mw when added to SOC was found to associate with significantly increased risk of mortality and increased length of hospital stay. However, time since admission to administration of Mw was a significant predictor of in-ICU deaths in multivariate analysis. Early initiation of Mw (<3 days) was observed to be a protective factor against ICU deaths from the multivariate logistic regression model. However, large randomized controlled trials are required to support the same.

A Practitioner's Toolkit for Polycystic Ovary Syndrome Counselling.

Polycystic ovary syndrome (PCOS), a frequently occurring health issue, has a significant effect on the cosmetic, metabolic, psychosocial and fertility aspects of women. A multidisciplinary team approach based on the core pillars of screening, assessment and counselling to detect, prevent and treat physiological and psychological issues in PCOS is very essential. Women are treated medically, but the psychosocial part is often forsaken. Hence, counselling forms an integral part of PCOS management that enables enhanced clinical outcomes and patient satisfaction. Digital tools and PCOS support groups have built an opportunity for physicians to create awareness, help timely diagnosis and overcome PCOS symptoms. The absence of clear guidelines to tackle the often less discussed aspects of PCOS warrants the need for consensus on PCOS counselling. This review summarizes the biopsychosocial health, clinical assessment and treatment strategies of PCOS and associated co-morbidities. The review article will discuss the clinician's role in patient education with the special focus on counselling of females with PCOS regardless of age group.

Management of Glucocorticoid-Induced Hyperglycemia.

Glucocorticoids are potent immunosuppressive and anti-inflammatory drugs used for various systemic and localized conditions. The use of glucocorticoids needs to be weighed against their adverse effect of aggravating hyperglycemia in persons with diabetes mellitus, unmask undiagnosed diabetes mellitus, or precipitate glucocorticoid-induced diabetes mellitus appearance. Hyperglycemia is associated with poor clinical outcomes, including infection, disability after hospital discharge, prolonged hospital stay, and death. Furthermore, clear guidelines for managing glucocorticoid-induced hyperglycemia are lacking. Therefore, this consensus document aims to develop guidance on the management of glucocorticoid-induced hyperglycemia. Twenty expert endocrinologists, in a virtual meeting, discussed the evidence and practical experience of real-life management of glucocorticoid-induced hyperglycemia. The expert group concluded that we should be proactive in terms of diagnosis, management, and post-steroid care. Since every patient has different severity of underlying disease, clinical stratification would help understand patient profiles and determine the treatment course. Patients at home with pre-existing diabetes who are already on oral or injectable therapy can continue the same as long as they are clinically stable and eating adequately. However, depending on the degree of hyperglycemia, modification of doses may be required. Initiating basal bolus with correction regimen is recommended for patients in non-intensive care unit settings. For patients in intensive care unit, variable rate intravenous insulin infusion could be temporarily used, but under supervision of diabetes inpatient team, and patients can be transitioned to subcutaneous insulin once stable baseline assessment and continual evaluation are crucial for day-to-day decisions concerning insulin doses. Glycemic variability should be carefully monitored, and interventions to treat patients should also aim at achieving and maintaining euglycemia. Rational use of glucose-lowering drugs is recommended and treatment regimen should ensure maximum safety for both patient and provider. Glucovigilance is required as the steroids taper during transition, and insulin dosage should be reduced subsequently. Increased clinical and economic burden resulting from corticosteroid-related adverse events highlights the need for effective management. Therefore, these recommendations would help successfully manage GC-induced hyperglycemia and judiciously allocate resources.

Endocrine Follow-up During Post-Acute COVID-19: Practical Recommendations Based on Available Clinical Evidence.

OBJECTIVE: COVID-19 affects multiple endocrine organ systems during the disease course. However, follow-up data post-COVID-19 is scarce; hitherto available limited data suggest that most of the biochemical endocrine dysfunctions observed during acute phase of COVID-19 tend to improve after recovery. Hence, we aim to provide a rational approach toward endocrine follow-up of patients during post-acute COVID-19. METHODS: We performed a literature review across PubMed/MEDLINE database looking into the effects of COVID-19 on endocrine system and subsequent long-term endocrine sequelae. Accordingly, we have presented a practical set of recommendations regarding endocrine follow-up post-acute COVID-19. RESULTS: COVID-19 can lead to new-onset hyperglycemia/diabetes mellitus or worsening of dysglycemia in patients with preexisting diabetes mellitus. Hence, those with preexisting diabetes mellitus should ensure optimum glycemic control in the post-COVID-19 period. New-onset diabetes mellitus has been described post-acute COVID-19; hence, a selected group of patients (aged <70 years and those requiring intensive care unit admission) may be screened for the same at 3 months. Thyroid dysfunction (euthyroid sick syndrome and atypical thyroiditis) and adrenal insufficiency have been described in COVID-19; however, thyroid/adrenal functions usually normalize on follow-up; hence, widespread screening post-acute COVID-19 should not be recommended. Pituitary apoplexy and male hypogonadism have rarely been documented in COVID-19; therefore, appropriate follow-up may be undertaken as per clinical context. Hypocalcemia during COVID-19 is not uncommon; however, routine estimation of serum calcium post-COVID-19 is not warranted. CONCLUSION: The recommendations herein provide a rational approach that would be expected to guide physicians to better delineate and manage the endocrine sequelae during post-acute COVID-19.

Clean intermittent catheterization in long-term management of neurogenic bladder in spinal cord injury: Patient perspective and experiences.

OBJECTIVES: Bladder dysfunction due to spinal cord injury has a significant impact on the overall health and quality of life of an individual. Clean intermittent catheterization is the gold standard for bladder management and is recommended due to having the lowest complication rate. Transitions from intermittent catheterization to other less optimal strategies, such as indwelling catheter, are quite common. However, the research documenting patient perspectives, and epidemiological and demographic factors related to such transition is limited. METHODS: Data from patients with spinal cord injury rehabilitated with clean intermittent catheterization were collected. Demographic and epidemiological details of the patients were documented from the inpatient records. Appropriate statistical tests were applied to the values. RESULTS: Among the 45 participants, 68.89% continued clean intermittent catheterization. In those who discontinued clean intermittent catheterization, the median duration of practicing clean intermittent catheterization was 3.5 months. The commonest difficulty among compliant patients was carrying out clean intermittent catheterization in outdoor environments due to the unavailability of toilet facilities. Urinary tract infection was the most common (17.78%) complication noted. Dependence (20.00%) was a major procedural difficulty followed by pain. Adaptations to remain continent in special conditions were diapers and condom catheters. The duration of clean intermittent catheterization practiced influenced discontinuation of clean intermittent catheterization. With an increase in the duration of clean intermittent catheterization practiced after discharge, the risk of discontinuation of clean intermittent catheterization decreased with an adjusted odds ratio of 0.773 (95% confidence interval 0.609-0.982). CONCLUSIONS: People with spinal cord injury have many challenging issues in the regulation of bladder function at their level inclusive of procedural difficulties, environmental barriers and medical complications, and understanding of which will help to establish a comprehensive and a holistic program to provide remote/community care.

A review through therapeutic attributes of Ayurvedic formulation mashi.

Mashi is a black colored powder formulation obtained after combustion of the plant or animal drug. It is prepared by bahirdhum padhati (outside) or anterdhum padhati (in the close vessel). In this dosage form, bulk of raw material is reduced to a greater extent by the application of a certain quantum of energy. Due to this treatment, hidden chemical constituents become prominent and/or a new chemical moiety is formed which is therapeutically active. This formulation is cost-effective and easy to prepare. This review article aims to highlight the different mashi formulations mentioned in Ayurvedic text and also incorporate the formulation not mentioned in the Ayurvedic text but used by Ayurvedic practitioners. The objective was to introduce researchers to the simple yet excellent formulation mashi which should be studied in detail to establish its identity, purity, and therapeutic activity.

Risk of Developing Type 2 Diabetes Mellitus in South Asian Women with History of Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis.

BACKGROUND: Gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (T2DM) represent two different components of the spectrum of diabetes mellitus (DM). Women with GDM have a high chance of developing T2DM in later life and this relative risk depends on a number of factors including ethnicity. AIM: To compare and estimate the risk of developing T2DM in South Asian women with a history of GDM compared to those without a history of GDM. METHODS: This is a systematic review of PubMed and MEDLINE articles reporting the progression of GDM to T2DM that were published in English from 2000 to 2020. We performed meta-analysis to calculate risk ratios (RR). RESULTS: We selected 6 studies considering the inclusion and exclusion criteria after sorting 25 full-text articles. Of the 44165 South Asian women assessed, 3095 had GDM and 41070 were without GDM. 995 women in GDM group and 1525 women in non-GDM group had developed T2DM. The RR of women with GDM over non-GDM in developing T2DM was 10.81 (95% confidence interval (CI): 7.61-15.35) suggesting that women with GDM are at 10.81 times more risk of developing T2DM than non-GDM. The cumulative incidence of T2DM in GDM group was 17.34% at 5 years of follow-up and 33% at more than 10 years of follow-up. CONCLUSION: The risk of developing T2DM in later life is higher in South Asian women with GDM than without GDM. Therefore, lifestyle and pharmacological interventions, patient communication, timely screening, and long-term follow-up of GDM patients are important to reduce the risk.

Quantifying Remission Probability in Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is a chronic progressive disorder and is associated with significant morbidity and mortality. The concept of T2DM remission and the reversal of diabetic parameters to normal levels has been gaining momentum over the past years. T2DM remission is increasingly being recognized by various global guidelines. Multiple models have been developed and validated for quantifying the extent of remission achieved. Based on favorable clinical evidence, T2DM remission can be considered as the therapeutic goal in diabetes management and, in select cases, as an alternative to expensive treatment options, which can be burdensome as T2DM progresses. This narrative review discusses the available strategies, such as lifestyle interventions, physical activity, bariatric surgery, medical nutrition therapy, and non-insulin glucose-lowering medications, for achieving T2DM remission. Although the concept of T2DM remission has emerged as a real-world option, effective implementation in routine clinical practice may not be feasible until long-term studies prove the efficacy of different approaches in this regard.

SGLT2-inhibition and Vascular Euphoria a Reconciliation of Vascular Health and Disease Homeostasis.

The concept of SGLT2-inhibition, once regarded as a non-physiological approach to glycemia control, now finds a foundational relevance in risk-modification for cardiovascular, kidney, and metabolic outcomes, spanning beyond type-2 diabetes. Major studies have proven meaningful improvements in various clinical outcomes, with different SGLT2-i agents. Apart from glycosuria, SGLT2-inhibition is associated with several patho-physiological effects, which may contribute to the clinical benefits seen with these agents. This narrative review is an attempt to appraise the different patho-physiological effects mediated by SGLT2-inhibition, based on contemporary evidence. The review classifies these effects in the acronym of EUPHORIA, and grades the possible relevance of each effect, in improving clinical outcomes.

An Expert Opinion on "Glycemic Happiness": Delineating the Concept and Determinant Factors for Persons with Type 2 Diabetes Mellitus.

The importance of the psychological impact of diabetes is globally well-documented. Evidence suggests that there is a high level of psychosocial burden of diabetes in India. Moreover, there is a lack of relevant knowledge among the patients and caregivers regarding the psychological impact of diabetes and how to cope with it, as compared to the majority of other countries. "Happiness of the patient" is an essential component of diabetes management, which potentially affects the treatment outcome, treatment adherence, self-care, and lifelong management of diabetes. Although several validated tools and scales exist for measuring psychological outcomes both in patients and physicians, tools to assess "happiness in diabetes care" are still lacking. With this background, an expert group meeting was held in India in September 2019, involving nine expert diabetologists and endocrinologists across the country to discuss the concept of "glycemic happiness". This article summarizes the expert opinion on the factors affecting psychological outcomes in diabetes, introduces the concept of glycemic happiness, describes available scales and tools to measure general happiness, and delineates the five sets of questionnaires developed with questions that may help correlate with "glycemic happiness". The questionnaires are based on a five-point Likert method. The experts also discussed and decided upon the study design for a proposed observational survey to assess glycemic happiness of persons with type 2 diabetes mellitus (T2DM) based on the developed five sets of questionnaires. Given the huge burden of diabetes in India, the introduction of the concept of glycemic happiness will help in the optimization of diabetes care in the country.